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Biased Histamine Signaling Selectively Gates Oral Fat Preference

54 Pages Posted: 4 Apr 2025 Publication Status: Under Review

See all articles by Yanrong Zheng

Yanrong Zheng

Zhejiang Chinese Medical University

Jie Liao

Zhejiang University

Zhuowen Fang

Zhejiang University

Xinyan Tang

Zhejiang University

Zhuchen Zhou

Zhejiang Chinese Medical University

Xinyue Zhao

Zhejiang Chinese Medical University

Menghan Li

Zhejiang Chinese Medical University

Mengting Liu

Zhejiang Chinese Medical University

Shujun Xu

Zhejiang University

Jiahui Chen

Zhejiang University

Lingyu Xu

Zhejiang Chinese Medical University

Yi Wang

Zhejiang Chinese Medical University - Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province

Yan Zhang

Zhejiang University - Department of Pathology

Weiwei Hu

Zhejiang University

Zhong Chen

Zhejiang Chinese Medical University - Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province; Zhejiang University

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Abstract

Distinct peripheral neural circuits perceive sugar and fat to guide nutritional value-based food preferences. While orosensory experiences also influence meal size, neural mechanisms underlying selective oral fat preference remain unclear. Our whole-brain activity mapping revealed a striking separation of high-fat diet (HFD) and high-sucrose diet-responsive neuronal ensembles within the paraventricular thalamus (PVT). Employing translating ribosome affinity purification, we identified histamine H3 receptor (H3R) as a marker of PVTHFD neurons. Manipulating H3R expression or histaminergic terminals in the PVT specifically affects HFD consumption. Histamine-mediated H3R activation increases PVTHFD neuronal excitability via G12/13 signaling. This histaminergic circuit integrates oral dietary cues from the mesencephalic nucleus of the trigeminal nerve, regulating fat-texture-response. These findings establish a novel role for PVT in gating oral fat preference and identify H3R-G12/13 axis as a potential target for precise fat-consumption control.

Note:
Funding Information: This work was supported by National Natural Science Foundation of China (U21A20418), the National Key R&D Program of China (2021ZD0202803, 2019YFA050880), and Zhejiang Provincial Natural Science Foundation (LD25H090002).

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: All procedures adhered to the guidelines of the Animal Advisory Committee of Zhejiang Chinese Medical University and the US National Institutes of Health Guidelines for the Care and Use of Laboratory Animals. The Animal Advisory Committee of Zhejiang Chinese Medical University approved all procedures (No. 15827).

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Suggested Citation

Zheng, Yanrong and Liao, Jie and Fang, Zhuowen and Tang, Xinyan and Zhou, Zhuchen and Zhao, Xinyue and Li, Menghan and Liu, Mengting and Xu, Shujun and Chen, Jiahui and Xu, Lingyu and Wang, Yi and Zhang, Yan and Hu, Weiwei and Chen, Zhong and Administrator, Sneak Peek, Biased Histamine Signaling Selectively Gates Oral Fat Preference. Available at SSRN: https://ssrn.com/abstract=5200740 or http://dx.doi.org/10.2139/ssrn.5200740
This version of the paper has not been formally peer reviewed.

Yanrong Zheng

Zhejiang Chinese Medical University ( email )

Hangzhou
China

Jie Liao

Zhejiang University ( email )

38 Zheda Road
Hangzhou, 310058
China

Zhuowen Fang

Zhejiang University ( email )

38 Zheda Road
Hangzhou, 310058
China

Xinyan Tang

Zhejiang University ( email )

38 Zheda Road
Hangzhou, 310058
China

Zhuchen Zhou

Zhejiang Chinese Medical University ( email )

Hangzhou
China

Xinyue Zhao

Zhejiang Chinese Medical University ( email )

Hangzhou
China

Menghan Li

Zhejiang Chinese Medical University ( email )

Hangzhou
China

Mengting Liu

Zhejiang Chinese Medical University ( email )

Hangzhou
China

Shujun Xu

Zhejiang University ( email )

38 Zheda Road
Hangzhou, 310058
China

Jiahui Chen

Zhejiang University ( email )

38 Zheda Road
Hangzhou, 310058
China

Lingyu Xu

Zhejiang Chinese Medical University ( email )

Hangzhou
China

Yi Wang

Zhejiang Chinese Medical University - Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province ( email )

Yan Zhang

Zhejiang University - Department of Pathology ( email )

Hangzhou, 310058
China

Weiwei Hu

Zhejiang University ( email )

38 Zheda Road
Hangzhou, 310058
China

Zhong Chen (Contact Author)

Zhejiang Chinese Medical University - Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province ( email )

Zhejiang University ( email )

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